Five years of change in adult twins: longitudinal changes of genetic and environmental influence on epigenetic clocks.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week (Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD (Ptrend = 0.011) and MCEs (Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (Pinteraction = 0.037). CONCLUSIONS: Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.

Prospective evaluation of the relevance of Epstein-Barr virus antibodies for early detection of nasopharyngeal carcinoma in Chinese adults.

BACKGROUND: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. METHODS: A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. RESULTS: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. CONCLUSIONS: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.

Incidence and mortality rates of 14 site-specific infectious diseases in 10 diverse areas of China: findings from China Kadoorie Biobank, 2006-2018.

BACKGROUND: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults. METHODS: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalised for any infectious disease. Descriptive analyses examined standardised incidence, mortality, and case fatality of infections. FINDINGS: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex-differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women. INTERPRETATION: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts. FUNDING: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.

Early adulthood BMI and cardiovascular disease: a prospective cohort study from the China Kadoorie Biobank.

BACKGROUND: The associations of early adulthood BMI with cardiovascular diseases have yet to be completely delineated. There is little reliable evidence about these associations among east Asian populations, that differ in fat distribution, disease patterns, and lifestyle factors from other populations. We aimed to study the associations between early adulthood BMI and cardiovascular diseases in a Chinese population, and the effect of midlife lifestyle factors on outcomes. METHODS: In this prospective analysis, we used data from the China Kadoorie Biobank, a large and long-term cohort from five urban areas and five rural areas, using participants aged 35-70 years. The primary outcome was the incidence of cardiovascular diseases as a group, ischaemic heart disease, haemorrhagic stroke, and ischaemic stroke, which were obtained mainly through linkage to disease registries and the national database for health insurance claims. Early adulthood BMI was assessed through self-report at baseline survey. We used Cox proportional hazards regression models to examine the prospective associations. We also undertook multiplicative and additive interaction analyses to investigate the potential modification effect of midlife healthy lifestyle factors (a combined score covering smoking, drinking, physical activity, and diet). FINDINGS: Participants were recruited for baseline survey between June, 2004, and July, 2008. During a median follow-up of 12·0 years (IQR 11·3-13·1), we documented 57 203 (15·9%) of incident cardiovascular diseases in 360 855 participants. After adjustment for potential confounders, monotonic dose-response associations were observed between higher early adulthood BMI and increased risks of incident cardiovascular diseases. Compared with an early adulthood BMI of 20·5-22·4 kg/m2 (the reference group), the hazard ratios for a BMI of less than 18·5 kg/m2 was 0·97 (95% CI 0·94-1·00), 18·5-20·4 kg/m2 was 0·97 (0·95-0·99), 22·5-23·9 kg/m2 was 1·04 (1·02-1·07), 24·0-25·9 kg/m2 was 1·12 (1·09-1·15), 26·0-27·9 kg/m2 was 1·19 (1·14-1·24), 28·0-29·9 kg/m2 was 1·34 (1·25-1·44), and ≥30·0 kg/m2 was 1·58 (1·42-1·75). Except for haemorrhagic stroke, lower early adulthood BMI (<20·5 kg/m2) was associated with decreased incident cardiovascular disease risks. No significant interaction was found between midlife healthy lifestyle factors and early adulthood BMI on cardiovascular disease risks. INTERPRETATION: Increased risks of cardiovascular disease incidence were found among participants with high early adulthood adiposity, including ischaemic heart disease, haemorrhagic stroke, and ischaemic stroke. Our findings suggest early adulthood as an important time to focus on weight management and obesity prevention for cardiovascular health later in life. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, and the Wellcome Trust.

Development and evaluation of a risk prediction tool for risk-adapted screening of colorectal cancer in China.

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

Temporal change in multimorbidity prevalence, clustering patterns, and the association with mortality: findings from the China Kadoorie Biobank study in Jiangsu Province.

Objectives: The characteristics of multimorbidity in the Chinese population are currently unclear. We aimed to determine the temporal change in multimorbidity prevalence, clustering patterns, and the association of multimorbidity with mortality from all causes and four major chronic diseases. Methods: This study analyzed data from the China Kadoorie Biobank study performed in Wuzhong District, Jiangsu Province. A total of 53,269 participants aged 30-79 years were recruited between 2004 and 2008. New diagnoses of 15 chronic diseases and death events were collected during the mean follow-up of 10.9 years. Yule's Q cluster analysis method was used to determine the clustering patterns of multimorbidity. A Cox proportional hazards model was used to estimate the associations of multimorbidity with mortalities. Results: The overall multimorbidity prevalence rate was 21.1% at baseline and 27.7% at the end of follow-up. Multimorbidity increased more rapidly during the follow-up in individuals who had a higher risk at baseline. Three main multimorbidity patterns were identified: (i) cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), (ii) respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), and (iii) mental, kidney and arthritis multimorbidity (neurasthenia, psychiatric disorders, chronic kidney disease, and rheumatoid arthritis). There were 3,433 deaths during the follow-up. The mortality risk increased by 24% with each additional disease [hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.20-1.29]. Compared with those without multimorbidity at baseline, both cardiometabolic multimorbidity and respiratory multimorbidity were associated with increased mortality from all causes and four major chronic diseases. Cardiometabolic multimorbidity was additionally associated with mortality from cardiovascular diseases and diabetes, with HRs of 2.64 (95% CI = 2.19-3.19) and 28.19 (95% CI = 14.85-53.51), respectively. Respiratory multimorbidity was associated with respiratory disease mortality, with an HR of 9.76 (95% CI = 6.22-15.31). Conclusion: The prevalence of multimorbidity has increased substantially over the past decade. This study has revealed that cardiometabolic multimorbidity and respiratory multimorbidity have significantly increased mortality rates. These findings indicate the need to consider high-risk populations and to provide local evidence for intervention strategies and health management in economically developed regions.

Dietary factors and patterns in relation to risk of later-onset ulcerative colitis in Chinese: A prospective study of 0.5 million people.

BACKGROUND: There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults. AIMS: To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese. METHODS: The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79. Dietary habits were assessed using food frequency questionnaires. Dietary patterns were derived by factor analysis with a principal component method. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.1 years, 312 cases of newly diagnosed UC were documented (median age of diagnosis 60.1 years). Egg consumption was associated with higher risk of UC (HR for daily vs. never or rarely: 2.29 [95% CI: 1.26-4.16]), while spicy food consumption was inversely associated with risk of UC (HR: 0.63 [0.45-0.88]). The traditional northern dietary pattern, characterised by high intake of wheat and low intake of rice, was associated with higher risk of UC (HR for highest vs. lowest quartile of score: 2.79 [1.93-4.05]). The modern dietary pattern, characterised by high intake of animal-origin foods and fruits, was associated with higher risk of UC (HR: 2.48 [1.63-3.78]). Population attributable fraction was 13.04% (7.71%-19.11%) for daily/almost daily consumption of eggs and 9.87% (1.94%-18.22%) for never/rarely consumption of spicy food. CONCLUSIONS: The findings highlight the importance of evaluating dietary factors and patterns in the primary prevention of later-onset UC in Chinese adults.

Association between epigenetic age and type 2 diabetes mellitus or glycemic traits: A longitudinal twin study.

Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) clocks representing the degree of aging and DunedinPACE representing the pace of aging. Prior studies have shown the associations between epigenetic aging and T2DM, but the results vary by epigenetic age metrics and people. This study explored the associations between epigenetic age metrics and T2DM or glycemic traits, based on 1070 twins (535 twin pairs) from the Chinese National Twin Registry. It also explored the temporal relationships of epigenetic age metrics and glycemic traits in 314 twins (157 twin pairs) who participated in baseline and follow-up visits after a mean of 4.6 years. DNA methylation data were used to calculate epigenetic age metrics, including PCGrimAge acceleration (PCGrimAA), PCPhenoAge acceleration (PCPhenoAA), DunedinPACE, and the longitudinal change rate of PCGrimAge/PCPhenoAge. Mixed-effects and cross-lagged modelling assessed the cross-sectional and temporal relationships between epigenetic age metrics and T2DM or glycemic traits, respectively. In the cross-sectional analysis, positive associations were identified between DunedinPACE and glycemic traits, as well as between PCPhenoAA and fasting plasma glucose, which may be not confounded by shared genetic factors. Cross-lagged models revealed that glycemic traits (fasting plasma glucose, HbA1c, and TyG index) preceded DunedinPACE increases, and TyG index preceded PCGrimAA increases. Glycemic traits are positively associated with epigenetic age metrics, especially DunedinPACE. Glycemic traits preceded the increases in DunedinPACE and PCGrimAA. Lowering the levels of glycemic traits may reduce DunedinPACE and PCGrimAA, thereby mitigating age-related comorbidities.

Association of lifestyle with reduced stroke risk in 41 314 individuals with diabetes: Two prospective cohort studies in China.

AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.

Correlates and consequences of atrial fibrillation in a prospective study of 25 000 participants in the China Kadoorie Biobank.

Aims: The prevalence of atrial fibrillation (AF) is positively correlated with prior cardiovascular diseases (CVD) and CVD risk factors but is lower in Chinese than Europeans despite their higher burden of CVD. We examined the prevalence and prognosis of AF and other electrocardiogram (ECG) abnormalities in the China Kadoorie Biobank. Methods and results: A random sample of 25 239 adults (mean age 59.5 years, 62% women) had a 12-lead ECG recorded and interpreted using a Mortara VERITAS™ algorithm in 2013-14. Participants were followed up for 5 years for incident stroke, ischaemic heart disease, heart failure (HF), and all CVD, overall and by CHA2DS2-VASc scores, age, sex, and area. Overall, 1.2% had AF, 13.6% had left ventricular hypertrophy (LVH), and 28.1% had ischaemia (two-thirds of AF cases also had ischaemia or LVH). The prevalence of AF increased with age, prior CVD, and levels of CHA2DS2-VASc scores (0.5%, 1.3%, 2.1%, 2.9%, and 4.4% for scores <2, 2, 3, 4, and ≥5, respectively). Atrial fibrillation was associated with two-fold higher hazard ratios (HR) for CVD (2.15; 95% CI, 1.71-2.69) and stroke (1.88; 1.44-2.47) and a four-fold higher HR for HF (3.79; 2.21-6.49). The 5-year cumulative incidence of CVD was comparable for AF, prior CVD, and CHA2DS2-VASc scores ≥ 2 (36.7% vs. 36.2% vs. 37.7%, respectively) but was two-fold greater than for ischaemia (19.4%), LVH (18.0%), or normal ECG (14.1%), respectively. Conclusion: The findings highlight the importance of screening for AF together with estimation of CHA2DS2-VASc scores for prevention of CVD in Chinese adults.

Proteomic Analyses in Diverse Populations Improved Risk Prediction and Identified New Drug Targets for Type 2 Diabetes.

OBJECTIVE: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases). Proteomic-based risk models were developed with discrimination, calibration, reclassification assessed using area under the curve (AUC), calibration plots, and net reclassification index (NRI), respectively. Two-sample Mendelian randomization (MR) analyses using cis-protein quantitative trait loci identified in a genome-wide association study of CKB and UK Biobank for specific proteins were conducted to assess their causal relevance for T2D, along with colocalization analyses to examine shared causal variants between proteins and T2D. RESULTS: Overall, 33 proteins were significantly associated (false discovery rate <0.05) with risk of incident T2D, including IGFBP1, GHR, and amylase. The addition of these 33 proteins to a conventional risk prediction model improved AUC from 0.77 (0.73-0.82) to 0.88 (0.85-0.91) and NRI by 38%, with predicted risks well calibrated with observed risks. MR analyses provided support for the causal relevance for T2D of ENTR1, LPL, and PON3, with replication of ENTR1 and LPL in Europeans using different genetic instruments. Moreover, colocalization analyses showed strong evidence (pH4 > 0.6) of shared genetic variants of LPL and PON3 with T2D. CONCLUSIONS: Proteomic analyses in Chinese adults identified novel associations of multiple proteins with T2D with strong genetic evidence supporting their causal relevance and potential as novel drug targets for prevention and treatment of T2D.

Predictive value of 8-year blood pressure measures in intracerebral hemorrhage risk over 5 years.

AIMS: The relationships between long-term blood pressure (BP) measures and intracerebral hemorrhage (ICH), as well as their predictive ability on ICH, were unclear. We aimed to investigate the independent associations of multiple BP measures with subsequent 5-year ICH risk, as well as the incremental value of these measures over a single-point BP measurement in ICH risk prediction. METHODS: We included 12,398 participants from the China Kadoorie Biobank (CKB) who completed three surveys every four to five years. The following long-term BP measures were calculated: mean, minimum, maximum, standard deviation, coefficient of variation, average real variability, and cumulative BP exposure (cumBP). Cox proportional hazard models were used to examine the associations between these measures and ICH. The potential incremental value of these measures in ICH risk prediction was assessed using Harrell's C statistics, continuous net reclassification improvement (cNRI), and relative integrated discrimination improvement (rIDI). RESULTS: The hazard ratios (95% confidence intervals) of incident ICH associated with per SD increase in cumSBP and cumDBP were 1.62 (1.25, 2.10) and 1.59 (1.23, 2.07), respectively. When cumBP was added to the conventional 5-year ICH risk prediction model, the C-statistic change was 0.009 (-0.001, 0.019), the cNRI was 0.267 (0.070, 0.464), and the rIDI was 18.2% (5.8%, 30.7%). Further subgroup analyses revealed a consistent increase in cNRI and rIDI in men, rural residents, and participants without diabetes. Other long-term BP measures showed no statistically significant associations with incident ICH and generally did not improve model performance. CONCLUSION: The nearly 10-year cumBP was positively associated with an increased 5-year risk of ICH and could significantly improve risk reclassification for the ICH risk prediction model that included single-point BP measurement.

This prospective cohort study of Chinese adults investigated the independent associations of multiple blood pressure (BP) measures with subsequent 5-year intracerebral hemorrhage (ICH) risk, as well as the incremental value of these measures over a single-point BP measurement in ICH risk prediction. The cumulative BP exposure (cumBP) was positively associated with subsequent 5-year risk of ICH, independent of the recent single-point SBP and DBP levels.The cumBP could improve the risk reclassification of the conventional 5-year ICH risk prediction model that included single-point BP measurement for all participants, as well as for men, rural residents, and participants without diabetes.

Variations in the Prevalence of Anemia of Varying Severity Among Urban Non-Pregnant Women - China, 2021.

What is already known about this topic?: Anemia is a significant public health issue affecting women globally. Prior studies in China predominantly concentrated on anemia in pregnant or reproductive-age women, leaving a gap in available data concerning anemia in non-pregnant women of all age groups in China. What is added by this report?: In 2021, the prevalence of anemia and moderate to severe anemia among women aged 18 years and older in urban China was 14.8% and 5.7%, respectively. Anemia prevalence exhibited significant variations based on factors such as age, body mass index (BMI), geographic location, and socioeconomic status. What are the implications for public health practice?: The strategy for addressing anemia should account for non-pregnant women aged 30-49 years and those aged 70 years and older, taking into consideration differences related to socioeconomic development and geography.

A genome-wide association study based on the China Kadoorie Biobank identifies genetic associations between snoring and cardiometabolic traits.

Despite the high prevalence of snoring in Asia, little is known about the genetic etiology of snoring and its causal relationships with cardiometabolic traits. Based on 100,626 Chinese individuals, a genome-wide association study on snoring was conducted. Four novel loci were identified for snoring traits mapped on SLC25A21, the intergenic region of WDR11 and FGFR, NAA25, ALDH2, and VTI1A, respectively. The novel loci highlighted the roles of structural abnormality of the upper airway and craniofacial region and dysfunction of metabolic and transport systems in the development of snoring. In the two-sample bi-directional Mendelian randomization analysis, higher body mass index, weight, and elevated blood pressure were causal for snoring, and a reverse causal effect was observed between snoring and diastolic blood pressure. Altogether, our results revealed the possible etiology of snoring in China and indicated that managing cardiometabolic health was essential to snoring prevention, and hypertension should be considered among snorers.

Associations of traditional cardiovascular risk factors with 15-year blood pressure change and trajectories in Chinese adults: a prospective cohort study.

OBJECTIVE: How traditional cardiovascular disease (CVD) risk factors are related to long-term blood pressure change (BPC) or trajectories remain unclear. We aimed to examine the independent associations of these factors with 15-year BPC and trajectories in Chinese adults. METHODS: We included 15 985 participants who had attended three surveys, including 2004-2008 baseline survey, and 2013-2014 and 2020-2021 resurveys, over 15 years in the China Kadoorie Biobank (CKB). We measured systolic and diastolic blood pressure (SBP and DBP), height, weight, and waist circumference (WC). We asked about the sociodemographic characteristics and lifestyle factors, including smoking, alcohol drinking, intake of fresh vegetables, fruits, and red meat, and physical activity, using a structured questionnaire. We calculated standard deviation (SD), cumulative blood pressure (cumBP), coefficient of variation (CV), and average real variability (ARV) as long-term BPC proxies. We identified blood pressure trajectories using the latent class growth model. RESULTS: Most baseline sociodemographic and lifestyle characteristics were associated with cumBP. After adjusting for other characteristics, the cumSBP (mmHg × year) increased by 116.9 [95% confidence interval (CI): 111.0, 122.7] for every 10 years of age. The differences of cumSBP in heavy drinkers of ≥60 g pure alcohol per day and former drinkers were 86.7 (60.7, 112.6) and 48.9 (23.1, 74.8) compared with less than weekly drinkers. The cumSBP in participants who ate red meat less than weekly was 29.4 (12.0, 46.8) higher than those who ate red meat daily. The corresponding differences of cumSBP were 127.8 (120.7, 134.9) and 70.2 (65.0, 75.3) for BMI per 5 kg/m 2 and WC per 10 cm. Most of the findings of other BPC measures by baseline characteristics were similar to the cumBP, but the differences between groups were somewhat weaker. Alcohol drinking was associated with several high-risk trajectories of SBP and DBP. Both BMI and WC were independently associated with all high-risk blood pressure trajectories. CONCLUSIONS: Several traditional CVD risk factors were associated with unfavorable long-term BPC or blood pressure trajectories in Chinese adults.

Association between weight change, waist circumference change, and the risk of nonalcoholic fatty liver disease in individuals with metabolically healthy overweight or obesity and metabolically unhealthy overweight or obesity.

BACKGROUND: This study aimed to explore and compare the effect of weight change, and waist circumference (WC) change, on the risk of nonalcoholic fatty liver disease (NAFLD) in individuals with metabolically healthy overweight or obesity (MHOW/O) and metabolically unhealthy overweight or obesity (MUOW/O) in a health check-up cohort in China. METHODS: 5625 adults with overweight or obesity, and free from NAFLD at baseline were included. Metabolically healthy was defined as not having any components of metabolic syndrome. Weight/WC changes were calculated as the relative difference between the first and second visits of check-up. NAFLD was assessed based on abdominal ultrasound. RESULTS: During a median follow-up of 2.1 (IQR: 1.1-4.3) years, 1849 participants developed NAFLD. In MHOW/O participants, the multivariable adjusted HRs (95 % CIs) for NAFLD in weight change ≤ -5.0 %, and - 4.9-- 1.0 % were 0.36 (0.23-0.59), 0.59 (0.43-0.80), respectively, compared to the weight stable group (-0.9% to 0.9 %). The corresponding HRs (95 % CIs) for the association between WC change (≤ 6.0 %, - 5.9 to -3.0 %) and NAFLD in MHOW/O participants were 0.41 (0.27-0.62), and 0.74 (0.54-1.01), respectively, compared to the WC stable group (-2.9-2.9 %). Similar patterns were observed in MUOW/O participants. A more marked gradient of cumulative incidence of NAFLD across weight/WC change categories was observed in MHOW/O than in MUOW/O individuals. CONCLUSIONS: A more evident association between weight/WC loss and risk of NAFLD was observed in MHOW/O than in MUOW/O individuals. Our findings indicate the practical significance of encouraging all individuals with overweight and obesity to achieve a clinically relevant level of weight/WC loss to prevent NAFLD, even among metabolic healthy groups.

Association between health insurance cost-sharing and choice of hospital tier for cardiovascular diseases in China: a prospective cohort study.

Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009-2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64-68% of stroke and IHD cases in urban areas and 27-29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.